A mood disorder, which is a mental disorder typified by depression and bipolar disorder, is recently becoming more prevalent and is becoming a major social problem. A mood disorder is basically treated by pharmacotherapy in which a tricyclic antidepressant, a selective serotonin reuptake inhibitor (SSRI), a serotonin and norepinephrine reuptake inhibitor (SNRI), and/or the like is/are used.
Human herpesvirus-6 (HHV-6) is a virus found in the peripheral blood of an AIDS patient, and belongs to a herpesvirus 13 subfamily. HHV-6 has two variants: HHV-6 variant A (HHV-6A) and HHV-6 variant B (HHV-6B). Most humans are initially infected by HHV-6B during infancy, and roseola infantum occurs at development of infection. At an acute stage of initial infection, HHV-6B is highly likely to invade into a brain and latently infect the brain. The latent infection remains even after an infected person becomes an adult (Non-Patent Literature 1). Latent infection means an infection state in which a virus remains in a host cell without producing infectious viral particles. It is suggested that in a brain, mainly glial cells of a frontal lobe, a hippocampal region, and the like contract HHV-6B latent infection (Non-Patent Literatures 2 and 3). In addition, macrophages in peripheral blood also suffer HHV-6 latent infection, and fatigue developed by daily living or the like causes the HHV-6 to be reactivated and released into saliva (Patent Literature 1).
During latent infection with HHV-6, no virus is produced. It is known, however, that there exists an “intermediate stage” which is a relatively stable stage and in which genes are actively expressed. As a protein expressed in an intermediate stage, (Small protein encoded by the Intermediate stage Transcript of HHV-6)-1 (hereinafter referred to as “SITH-1”) is identified (Patent Literature 2). Since an antibody against SITH-1 is detected specifically in a patient of a mood disorder such as depression, a method for diagnosing a mood disorder has been developed, which method includes detecting and measuring an anti-SITH-1 antibody in a specimen from a human subject (Patent Literature 2). It was also disclosed that in a case where a SITH-1 gene, which was linked to a glial cell-specific expression promoter, was introduced into the brain of a mouse with use of an adenovirus vector and was expressed, the mouse exhibited behavioral abnormalities such as those caused by a mental disorder (Patent Literature 2).
Calcium-signal modulating cyclophilin ligand (CAML) is originally isolated as an endoplasmic reticulum membrane protein that regulates T cell receptor signaling. CAML is subsequently found to function as a TRC40 receptor in an endoplasmic reticulum membrane (Non-Patent Literature 4). It has been known that CAML is strongly expressed in lymphocytes and in a brain, and has a function to increase an intracellular calcium concentration when strongly bound to SITH-1 in a cell (Patent Literature 2).